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Stress related proteases in Caulobacter crescentus

新月柄杆菌中应激相关的蛋白酶

基本信息

批准号：
9705784
负责人：
Peter Chien
金额：
$ 6.25万
依托单位：
UNIVERSITY OF MASSACHUSETTS AMHERST
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-01 至 2019-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9705784
关键词：
Address Affect Antibiotics Bacteria Binding Biochemical Genetics Biological Caulobacter Caulobacter crescentus Cell Cycle Arrest Cell Cycle Regulation Cells Characteristics Client Closure by clamp Complex DNA Damage DNA biosynthesis Development Elements Environment Escherichia coli Genetic Transcription Growth Health Human In Vitro Invaded Kinetics Link Modeling Molecular Chaperones Nucleotides Pathogenicity Pathway interactions Peptide Hydrolases Peptides Play Process Production Protein Isoforms Proteins Proteolysis Proteomics Quality Control Resources Rest Role Signal Transduction Slide Stress Testing Virulence Work biological adaptation to stress endopeptidase La improved in vivo insight misfolded protein novel pathogen predictive test prevent protein degradation protein folding protein misfolding proteotoxicity public health relevance repaired response stress tolerance tau Proteins

项目摘要

Project Summary Bacteria use energy dependent proteases to respond to stressful conditions. These proteases serve a dual role: destroying aberrant, potentially toxic, damaged proteins and generating stress responsive signals through degradation of regulatory factors. Cells often arrest replication in response to stress, but how regulated prote- olysis contributes to cell cycle arrest in bacteria is currently poorly understood. This proposal addresses how stress related proteases target replication factors using a combination of biochemical, genetic and proteomic approaches, specifically focusing on proteases and replication factors from the model bacteria Caulobacter crescentus. Aims 1 and 2 determine how misfolded proteins generated during proteotoxic stress directly stimu- late the Lon protease to destroy the replication initiator DnaA and cause growth arrest during stress. Aims 3 and 4 focus on how partial processing of the clamp loader subunit DnaX by the ClpXP protease is critical for replication stress tolerance during DNA damage. Because these proteases and replication factors are highly conserved throughout all bacteria, these results will impact our general understanding of replication, proteoly- sis, and stress tolerance. The critical role of these proteases in bacterial virulence and pathogenicity, together with the universal requirement for these proteases in bacterial stress responses, suggests that they are excel- lent targets for development of new antibiotic strategies that are of immediate human health need.

项目总结

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

An Adaptor Hierarchy Regulates Proteolysis during a Bacterial Cell Cycle.

DOI：
10.1016/j.cell.2015.09.030
发表时间：
2015-10-08
期刊：
Cell
影响因子：
64.5
作者：
Joshi KK;Bergé M;Radhakrishnan SK;Viollier PH;Chien P
通讯作者：
Chien P

Regulated Proteolysis in Bacteria: Caulobacter.

DOI：
10.1146/annurev-genet-120215-035235
发表时间：
2016-11-23
期刊：
Annual review of genetics
影响因子：
11.1
作者：
Joshi KK;Chien P
通讯作者：
Chien P

Sinorhizobium meliloti CtrA Stability Is Regulated in a CbrA-Dependent Manner That Is Influenced by CpdR1

苜蓿中华根瘤菌 CtrA 稳定性以 CbrA 依赖性方式调节，并受 CpdR1 影响

DOI：
10.1128/jb.02593-14
发表时间：
2015
期刊：
Journal of Bacteriology
影响因子：
3.2
作者：
Schallies, Karla B.;Sadowski, Craig;Meng, Julia;Chien, Peter;Gibson, Katherine E.
通讯作者：
Gibson, Katherine E.

Not Throwing Baby Out with the Bathwater.

不要把婴儿和洗澡水一起倒掉。